Unravelling the endosomal escape of pH-responsive nanoparticles using the split luciferase endosomal escape quantification assay

Abstract

Endosomal escape is a major bottleneck for efficient intracellular delivery of therapeutic cargoes, particularly for macromolecular biological cargoes such as peptides, proteins and nucleic acids. pH-responsive polymeric nanoparticles that can respond to changes in the pH of intracellular microenvironments have generated substantial interest in navigating the endosomal barrier. In this study, we applied the highly sensitive split luciferase endosomal escape quantification (SLEEQ) assay to better understand the endosomal escape efficiency of dual component pH-responsive nanoparticles based on poly(2-(diethylamino) ethyl methacrylate) (PDEAEMA) and poly(2-(diisopropylamino) ethyl methacrylate)..